Chlamydia developmental cycle regulation by a novel transcriptional repressor

University Of Kansas Lawrence, Lawrence KS

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Abstract

DESCRIPTION (provided by applicant): Chlamydia are human pathogens that cause sterility, blindness, pneumonia, and are strongly correlated with the number one cause of death in humans, heart disease. Chlamydia are obligate intracellular bacteria that are perpetuated through a defining bi-phasic developmental cycle that includes phenotypically and functionally distinct forms. The developmental cycle of Chlamydia is intimately linked with pathogenesis. The developmental cycle is governed predominately at the transcriptional level;however, there is a critical deficiency in our understanding of developmental regulatory mechanisms in Chlamydia. Identifying these components and characterizing the mechanisms is critical for understanding how Chlamydia modulates progression of the virulence defining developmental cycle and eventual generation of novel antimicrobial targets. Chlamydia encode a putative transcriptional regulator termed YfgA that is hypothesized to have an important role in regulating Chlamydia development and virulence determinant expression. Our Specific Aims for this proposal include: (1) Delineate the expression patterns of YfgA throughout the developmental cycle of Chlamydia, (2) Determine DNA recognition sites of YfgA, and (3) Define the quaternary structure of YfgA. The research proposed in this application is significant because it will provide critical preliminary observations for defining the biological role and regulatory mechanism of YfgA in the developmental cycle of Chlamydia. PUBLIC HEALTH RELEVANCE: Proposed studies will facilitate our understanding of how and what controls development and disease for the medically important bacteria, Chlamydia. Defining the biological role and regulatory mechanism is critical for future development of new anti-microbials to combat human chlamydial infections.